Can Addition of T-DM1 Improve Outcomes Over Standard Treatment in HER2-Positive Breast Cancer?

By: Vanessa A. Carter, BS
Posted: Thursday, May 5, 2022

The phase III KAITLIN study, conducted by Ian E. Krop, MD, of the Dana-Farber Cancer Institute, Harvard Medical School, Boston, and colleagues aimed to improve the efficacy and safety of treatment for high-risk HER2-positive breast cancer by replacing taxanes and trastuzumab with trastuzumab emtansine (T-DM1). Published in the Journal of Clinical Oncology, these results concluded that although both arms reached a favorable invasive disease–free survival, the combination of trastuzumab, pertuzumab, and chemotherapy remains the standard of care for this disease.

This multinational, open-label trial enrolled 1,846 adults with excised HER2-positive early breast cancer with node-positive (n = 1,658) disease. Participants were randomly assigned to receive three to four cycles of anthracycline-based chemotherapy and then 18 cycles of T-DM1 plus pertuzumab (AC-KP; n = 928), or three to four cycles of taxane plus trastuzumab plus pertuzumab (AC-THP; n = 918). Adjuvant endocrine therapy and/or radiotherapy was allowed.

At the median follow-up of 57.1 months for AC-THP and 57.0 months for AC-KP, there appeared to be no significant difference in invasive disease–free survival between the node-positive group (hazard ratio [HR] = 0.97) and the overall (HR = 0.98) population. Of note, the 3-year invasive disease–free survival rates were also similar among patients in the overall population who received AC-THP (94.2%) or AC-KP (93.1%).

The treatment completion rate was higher among patients administered AC-THP versus AC-KP (88.4% vs. 65.0%), which was thought to be due to laboratory abnormalities leading to T-DM1 discontinuation. Notably, both the AC-THP and AC-KP treatment arms experienced similar rates of grade 3 or higher adverse events (55.4% vs. 51.8%) or adverse events considered to be serious (23.3% vs. 21.4%). Furthermore, treatment with T-DM1 plus pertuzumab was observed to decrease clinically meaningful deterioration in global health status versus the combination of taxane, trastuzumab, and pertuzumab (HR = 0.71).

Disclosure: For full disclosures of the study authors, visit ascopubs.org.

Journal of Clinical Oncology